Electroporation system and method of energizing a catheter

ABSTRACT

The present disclosure provides electroporation systems and methods of energizing a catheter for delivering electroporation. A catheter for delivering electroporation includes a distal section and an electrode assembly. The distal section is configured to be positioned in a vein within a body. The vein defines a central axis. The electrode assembly is coupled to the distal section and includes a structure and a plurality of electrodes distributed thereabout. The structure is configured to at least partially contact the vein. Each of the electrodes is configured to be selectively energized to form a circumferential ring of energized electrodes that is concentric with the central axis of the vein.

CROSS REFERENCE OF RELATED APPLICATION

This application is a continuation of U.S. Non-Provisional applicationSer. No. 16/493,336, filed on Sep. 12, 2019, which is the national stageentry of PCT/US2018/026679, filed on Apr. 9, 2018, which claims thebenefit of priority to U.S. Provisional Application Ser. No. 62/483,749,filed Apr. 10, 2017, all of which are incorporated by reference hereinin their entirety.

FIELD OF THE DISCLOSURE

The present disclosure relates generally to medical devices that areused in the human body. In particular, in many embodiments, the presentdisclosure relates to electroporation systems and methods of energizinga catheter for delivering electroporation.

BACKGROUND

It is generally known that ablation therapy may be used to treat variousconditions afflicting the human anatomy. One such condition in whichablation therapy finds a particular application in, for example, is thetreatment of atrial arrhythmias. When tissue is ablated, or at leastsubjected to ablative energy generated by an ablation generator anddelivered by an ablation catheter, lesions form in the tissue.Electrodes mounted on or in ablation catheters are used to create tissuenecrosis in cardiac tissue to correct conditions such as atrialarrhythmia (including, but not limited to, ectopic atrial tachycardia,atrial fibrillation, and atrial flutter). Arrhythmia (i.e., irregularheart rhythm) can create a variety of dangerous conditions includingloss of synchronous atrioventricular contractions and stasis of bloodflow that can lead to a variety of ailments and even death. It isbelieved that the primary cause of atrial arrhythmia is stray electricalsignals within the left or right atrium of the heart. The ablationcatheter imparts ablative energy (e.g., radio frequency energy,cryoablation, lasers, chemicals, high-intensity focused ultrasound,etc.) to cardiac tissue to create a lesion in the cardiac tissue. Thislesion disrupts undesirable electrical pathways and thereby limits orprevents stray electrical signals that lead to arrhythmias.

One candidate for use in therapy of cardiac arrhythmias iselectroporation. Electroporation therapy involves electric field inducedpore formation on the cell membrane. The electric field may be inducedby applying a direct current (DC) signal delivered as a relatively shortduration pulse that may last, for instance, from a nanosecond to severalmilliseconds. Such a pulse may be repeated to form a pulse train. Whensuch an electric field is applied to tissue in an in vivo setting, thecells in the tissue are subjected to trans-membrane potential, whichopens the pores on the cell wall, hence the term electroporation.Electroporation may be reversible (i.e., the temporally-opened poreswill reseal) or irreversible (i.e., the pores will remain open). Forexample, in the field of gene therapy, reversible electroporation (i.e.,temporarily open pores) is used to transfect high molecular weighttherapeutic vectors into the cells. In other therapeutic applications, asuitably configured pulse train alone may be used to cause celldestruction, for instance by causing irreversible electroporation.

BRIEF SUMMARY OF THE DISCLOSURE

The present disclosure generally relates to electroporation systems andmethods of energizing a catheter for delivering electroporation. In manyembodiments, the electroporation system includes a catheter connected toa direct current (DC) energy source. The catheter and DC energy sourceare further connected to a computing system that, in certainembodiments, enables three-dimensional or two-dimensional visualizationof the catheter within a vein of a body. The catheter includes anelectrode assembly having a structure about which a plurality ofelectrodes is distributed. The structure may include, for example, ahoop catheter, a basket catheter, or a balloon catheter. The electrodesmay include, for example, flexible circuits, printed electrodes, or ringelectrodes. In many embodiments, the computing system determinespositioning of the catheter in the vein and controls the DC energysource to energize selected electrodes of the plurality. The selectionof the electrodes, in certain embodiments, is automatic. In otherembodiments, the selection of electrodes is made by a clinician orphysician based on a visualization. The selected electrodes to beenergized form a ring of electrodes that is concentric with a centralaxis of the vein in which the catheter is positioned. Other embodimentsand descriptions of the present disclosure are set forth below.

In one embodiment, the present disclosure provides a catheter fordelivering electroporation. The catheter includes a distal section andan electrode assembly. The distal section is configured to be positionedin a vein within a body. The vein defines a central axis. The electrodeassembly is coupled to the distal section and includes a structure and aplurality of electrodes distributed thereabout. The structure isconfigured to at least partially contact the vein. Each of theelectrodes is configured to be selectively energized to form acircumferential ring of energized electrodes that is concentric with thecentral axis of the vein.

In another embodiment, the present disclosure is directed to anelectroporation system, including a catheter, a DC energy source, and acomputing system. The catheter includes an electrode assembly configuredto be positioned in a vein of a body. The vein defines a central axis.The electrode assembly includes a structure configured to at leastpartially contact the vein, and a plurality of electrodes distributedabout the structure. Each electrode of the plurality of electrodes isconfigured to be individually energized. The DC energy source is coupledto the catheter and is configured to selectively energize a subset ofelectrodes of the plurality of electrodes. The computing system iscoupled to the catheter and the DC energy source. The computing systemconfigured to detect respective positions of the plurality of electrodeswithin the vein, and select the subset of electrodes to form acircumferential ring of energized electrodes that is concentric with thecentral axis of the vein.

In another embodiment, the present disclosure is directed to a method ofenergizing a catheter. The method includes positioning a distal sectionof the catheter relative to a central axis in space. The distal sectionincludes a plurality of electrodes distributed about a structure, andthe structure at least partially surrounds the central axis. The methodincludes determining respective locations of the plurality of electrodesrelative to the central axis. The method includes selecting a subset ofelectrodes from among the plurality of electrodes based on therespective locations thereof to form a circumferential ring ofelectrodes that is concentric with the central axis. The method includesenergizing the subset of electrodes.

The foregoing and other aspects, features, details, utilities andadvantages of the present disclosure will be apparent from reading thefollowing description and claims, and from reviewing the accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic and block diagram view of a system incorporatingembodiments for electroporation therapy;

FIG. 2 is a schematic diagram of an exemplary basket catheter for use inthe electroporation system shown in FIG. 1 ;

FIG. 3 is a schematic diagram of an exemplary visualization of thebasket catheter shown in FIG. 2 ;

FIG. 4 is a schematic diagram of an exemplary balloon catheter for usein the electroporation system shown in FIG. 1 ;

FIG. 5 is a schematic diagram of an exemplary helical catheter for usein the electroporation system shown in FIG. 1 ;

FIG. 6 is a flow diagram of an exemplary method of energizing thecatheters shown in FIGS. 1-5 ; and

FIG. 7 is a plot illustrating an exemplary intersection of a planerepresenting a pulmonary vein and an ellipsoid representing a catheter.

Corresponding reference characters indicate corresponding partsthroughout the several views of the drawings. It is understood that thatFigures are not necessarily to scale.

DETAILED DESCRIPTION OF THE DISCLOSURE

The present disclosure relates generally to medical devices that areused in the human body. In particular, in many embodiments, the presentdisclosure relates to electroporation systems and methods of energizinga catheter for delivering irreversible electroporation (IRE) usingintracardiac catheters, such as, for example, a spiral catheter, or“voltage” catheter, that delivers a high-voltage to multiple electrodesthrough which a therapeutic current flows into a pulmonary vein of theleft atrium of the heart. During such a procedure, a physician maneuversthe catheter to place it the ostia or antrum of a pulmonary vein. Thecatheter should be oriented, preferably, such that a hoop of thecatheter is concentric with the central axis of the pulmonary vein. Itis realized herein that achieving such an orientation is challenging,potentially requiring multiple attempts and, in certain circumstances, aproper position and orientation of the catheter cannot be achieved. Itis further realized herein that it is desirable to simplify the task ofplacing the catheter for better concentricity and to reduce the time toplace the catheter. It is also desirable to ensure the electrodes of thecatheter contact the cardiac tissue. Contact can be difficult to achievedue to the variable shape and eccentricity of pulmonary veins, thecomplexity of the endocardium and entrance to the pulmonary veins, anddue to the catheter's circular shape and limited ability to deform.

Embodiments of the electroporation systems described herein provide acatheter having a constellation of electrodes that, when placed in thepulmonary vein and mapped, are selectively energized to form a ring ofelectrodes concentric with the central axis of the pulmonary vein andthrough which a therapeutic IRE current is delivered. The catheter ismapped by a navigation system that, in certain embodiments, provides avisualization and interface for the physician. In certain embodiments,the catheter is a basket catheter that can be placed in a collapsedstate such that it can be maneuvered as a linear catheter. Such acatheter is then expanded within the pulmonary vein to ensure contactaround a full circumference of the pulmonary vein. The selected ring ofelectrodes establishes a virtual ring or virtual spiral of electrodesthat is as operably effective at delivering IRE current as an ideallyplaced hoop or spiral catheter, but with substantially greater ease inplacement. It is contemplated, however, that the described features andmethods of the present disclosure as described herein may beincorporated into any number of systems as would be appreciated by oneof ordinary skill in the art based on the disclosure herein.

Referring now to the drawings, FIG. 1 is a diagrammatic and blockdiagram view of a system 10 for electroporation therapy. In general, thevarious embodiments include an electrode assembly disposed at the distalsection of a catheter. As used herein, “proximal” refers to a directiontoward the end of the catheter near the clinician and “distal” refers toa direction away from the clinician and (generally) inside the body of apatient. The “distal section” of the catheter refers generally to thesection of the catheter, at or near the distal end, that is insertedinto the body of the patient. Moreover, embodiments described herein arenot limited to those having electrode assemblies disposed at the distalend of the catheter, and instead include embodiments where the catheter,in the distal region, extends beyond the electrode assembly in thedistal direction by some length. The electrode assembly includes one ormore individual, electrically-isolated electrode elements. Eachelectrode element, also referred to herein as a catheter electrode, isindividually wired such that it can be selectively paired or combinedwith any other electrode element to act as a bipolar or a multi-polarelectrode.

System 10 may be used for irreversible electroporation to destroytissue. In particular, system 10 may be used for electroporation-inducedprimary necrosis therapy, which refers to the effects of deliveringelectrical current in such manner as to directly cause an irreversibleloss of plasma membrane (cell wall) integrity leading to its breakdownand cell necrosis. This mechanism of cell death may be viewed as an“outside-in” process, meaning that the disruption of the outside wall ofthe cell causes detrimental effects to the inside of the cell.Typically, for classical plasma membrane electroporation, electriccurrent is delivered as a pulsed electric field in the form ofshort-duration direct current (DC) pulses (e.g., 0.1 to 20 ms duration)between closely spaced electrodes capable of delivering an electricfield strength of about 0.1 to 1.0 kV/cm.

Irreversible electroporation through a multi-electrode hoop catheter mayenable pulmonary vein isolation in as few as one shock per vein, whichmay produce much shorter procedure times compared to sequentiallypositioning a radiofrequency (RF) ablation tip around a vein.

It should be understood that while the energization strategies aredescribed as involving DC pulses, embodiments may use variations andremain within the spirit and scope of the invention. For example,exponentially-decaying pulses, exponentially-increasing pulses, andcombinations may be used.

It should be understood that the mechanism of cell destruction inelectroporation is not primarily due to heating effects, but rather tocell membrane disruption through application of a high-voltage electricfield. Thus, electroporation may avoid some possible thermal effectsthat may occur when using radio frequency (RF) energy. This “coldtherapy” thus has desirable characteristics.

With this background, and now referring again to FIG. 1 , system 10includes a catheter electrode assembly 12 including a constellation, orarray, of catheter electrodes configured to be used as briefly outlinedabove and as described in greater detail below. Electrode assembly 12 isincorporated as part of a medical device such as a catheter 14 forelectroporation therapy of tissue 16 in a body 17 of a patient. In theillustrative embodiment, tissue 16 comprises heart or cardiac tissue. Itshould be understood, however, that embodiments may be used to conductelectroporation therapy with respect to a variety of other body tissues.

FIG. 1 further shows a plurality of return electrodes designated 18, 20,and 21, which are diagrammatic of the body connections that may be usedby the various sub-systems included in the overall system 10, such as anelectroporation generator 26, an electrophysiology (EP) monitor such asan ECG monitor 28, and a localization and navigation system 30 forvisualization, mapping and navigation of internal body structures. Inthe illustrated embodiment, return electrodes 18, 20, and 21 are patchelectrodes. It should be understood that the illustration of a singlepatch electrode is diagrammatic only (for clarity) and that suchsub-systems to which these patch electrodes are connected may, andtypically will, include more than one patch (body surface) electrode. Inother embodiments, return electrodes 18, 20, and 21 may be any othertype of electrode suitable for use as a return electrode including, forexample, the constellation of catheter electrodes. Return electrodesthat are catheter electrodes may be part of electrode assembly 12 orpart of a separate catheter (not shown). System 10 may further include acomputer system 32 (including an electronic control unit 50 and datastorage—memory 52) integrated with localization and navigation system 30in certain embodiments. Computer system 32 may further includeconventional interface components, such as various user input/outputmechanisms 34 a and a display 34 b, among other components.

Electroporation generator 26 is configured to energize the electrodeelement(s) in accordance with an electroporation energization strategythat may be predetermined or may be user-selectable. The electrodeelements may include unipole electrodes, bipole electrodes, or acombination of both. For electroporation-induced primary necrosistherapy, generator 26 may be configured to produce an electric currentthat is delivered via electrode assembly 12 as a pulsed electric fieldin the form of short-duration DC pulses (e.g., a nanosecond to severalmilliseconds duration, 0.1 to 20 ms duration, or any duration suitablefor electroporation) between closely spaced electrodes capable ofdelivering an electric field strength (i.e., at the tissue site) ofabout 0.1 to 1.0 kV/cm. The amplitude and pulse duration needed forirreversible electroporation are inversely related. As pulse durationsare decreased, the amplitude is increased to achieve electroporation.

Electroporation generator 26, sometimes referred to herein as a DCenergy source, is a monophasic electroporation generator 26 configuredto generate a series of DC energy pulses that all produce current in thesame direction. In other embodiments, electroporation generator isbiphasic or polyphasic electroporation generator configured to produceDC energy pulses that do not all produce current in the same direction.For successful electroporation, some embodiments utilize a two hundredjoule output level. Electroporation generator 26 may output a DC pulsehaving a peak magnitude of between about negative one kilovolt (kV) andabout negative two kV at the two hundred joule output level. In someembodiments, electroporation generator 26 outputs a DC pulse having apeak magnitude between about negative 1.5 kV and about negative 2.0 kV.Other embodiments may output any other suitable voltage, including apositive voltage. In some embodiments, electroporation generator 26 is amonophasic defibrillator such as, for example, a Lifepak 9 defibrillatoravailable from Physio-Control, Inc., of Redmond, Wash., USA.

With continued reference to FIG. 1 , as noted above, catheter 14 maycomprise functionality for electroporation and in certain embodimentsalso an ablation function (e.g., RF ablation). It should be understood,however, that in those embodiments, variations are possible as to thetype of ablation energy provided (e.g., cryoablation, ultrasound, etc.).

In the illustrative embodiment, catheter 14 includes a cable connectoror interface 40, a handle 42, and a shaft 44 having a proximal end 46and a distal section 48. Catheter 14 may also include other conventionalcomponents not illustrated herein such as a temperature sensor,additional electrodes, and corresponding conductors or leads. Theconnector 40 provides mechanical and electrical connection(s) for cable56 extending from generator 26. The connector 40 may compriseconventional components known in the art and as shown is disposed at theproximal end of catheter 14.

Handle 42 provides a location for the clinician to hold catheter 14 andmay further provide means for steering or guiding shaft 44 within body17. For example, handle 42 may include means to change the length of aguidewire extending through catheter 14 to distal section 48 of shaft 44or means to steer shaft 44 to place electrode assembly 12 in a preferredlocation and orientation in the pulmonary vein. Moreover, in someembodiments, handle 42 may be configured to vary the shape, size, and/ororientation of a portion of the catheter. For example, where distalsection 48 includes a balloon or basket catheter, handle 42 may beconfigured to transition distal section 48 from a collapsed state to anexpanded state. Handle 42 is also conventional in the art and it will beunderstood that the construction of handle 42 may vary. In an alternateexemplary embodiment, catheter 14 may be robotically driven orcontrolled. Accordingly, rather than a clinician manipulating a handleto advance/retract and/or steer or guide catheter 14 (and shaft 44thereof in particular), a robot is used to manipulate catheter 14.

Shaft 44 is an elongated, tubular, flexible member configured formovement within body 17. Shaft 44 is configured to support electrodeassembly 12 as well as contain associated conductors, and possiblyadditional electronics used for selecting electrodes to be energized,signal processing, or conditioning. Shaft 44 may also permit transport,delivery and/or removal of fluids (including irrigation fluids andbodily fluids), medicines, and/or surgical tools or instruments. Shaft44 may be made from conventional materials such as polyurethane anddefines one or more lumens configured to house and/or transportelectrical conductors, fluids or surgical tools. Shaft 44 may beintroduced into a blood vessel or other structure within body 17 througha conventional introducer. Shaft 44 may then be advanced/retractedand/or steered or guided through body 17 to a desired location such asthe site of tissue 16, including through the use of guidewires or othermeans known in the art.

Shaft 44 houses electrode wires (not shown) for carrying electricalcurrent to the electrodes and conducting electrogram signals received bythe electrodes. Electrode wires extend between handle 42 and theelectrodes within an interior portion of shaft 44. To this end, shaft 44may include an insulator or insulating material. For example, shaft 44may be packed with an insulation material and/or a cylindrical layer ofinsulation material may be circumferentially disposed within an interiorportion of shaft 44. The thickness and material characteristics of suchinsulation are selected to configure shaft 44 for safe use with voltageand current in the range of one thousand volts and/or ten amperes.

In some embodiments, catheter 14 is a hoop catheter, sometimes referredto as a spiral catheter, where electrode assembly 12 includes catheterelectrodes (not shown) distributed about a structure of one or morehoops at distal section 48 of shaft 44. The diameter of the hoop(s) mayvary. In some embodiments, the hoop catheter has a maximum diameter ofabout twenty-seven millimeters (mm). In some embodiments, the hoopdiameter is variable between about fifteen mm and about twenty eight mm.Alternatively, the catheter may be a fixed diameter hoop catheter or maybe variable between different diameters. In some embodiments, catheter14 has fourteen catheter electrodes. In other embodiments, catheter 14includes ten catheter electrodes, twenty catheter electrodes, or anyother suitable number of electrodes for performing electroporation. Insome embodiments, the catheter electrodes are ring electrodes.Alternatively, the catheter electrodes may be any other suitable type ofelectrodes, such as single sided electrode or electrodes printed on aflex material. In various embodiments, the catheter electrodes havelengths of 1.0 mm, 2.0 mm, 2.5 mm, and/or any other suitable length forelectroporation.

In an alternative embodiment, catheter 14 is a basket catheter, whereelectrode assembly 12 includes catheter electrodes (not shown)distributed about multiple splines at distal section 48 of shaft 44. Thenumber, diameter, and eccentricity of the splines may vary. In someembodiments, the basket catheter includes eight splines. In otherembodiments, the basket catheter includes between twelve and sixteensplines. As the number of splines increases, the angular spacing betweeneach catheter electrode is reduced. However, an increased number ofsplines, and therefore electrodes, require additional wires tosufficiently connect electrode assembly 12 to handle 42 and interface40. In some embodiments, with an increased number of splines, the numberof electrodes per spline is reduced and more concentrated about theequator or within a band centered about the equator and extending, forexample, plus or minus 45 degrees in latitude. In yet anotheralternative embodiment, catheter 14 is a balloon catheter, whereelectrode assembly 12 includes catheter electrodes (not shown)distributed about a balloon at distal section 48 of shaft 44.

Localization and navigation system 30 may include a visualization systemfor visualization, mapping, and navigation of internal body structures.System 30 may comprise conventional apparatus known generally in the art(e.g., an EnSite NAVX™ Navigation and Visualization System, commerciallyavailable from St. Jude Medical, Inc. and as generally shown withreference to commonly assigned U.S. Pat. No. 7,263,397 titled “Methodand Apparatus for Catheter Navigation and Location and Mapping in theHeart,” the entire disclosure of which is incorporated herein byreference). It should be understood, however, that this system isexemplary only and not limiting in nature. Other technologies forlocating/navigating a catheter in space (and for visualization) areknown, including for example, the CARTO navigation and location systemof Biosense Webster, Inc., the AURORA® system of Northern Digital Inc.,commonly available fluoroscopy systems, or a magnetic location systemsuch as the gMPS system from Mediguide Ltd. In this regard, some of thelocalization, navigation and/or visualization system would involve asensor be provided for producing signals indicative of catheter locationinformation, and may include, for example one or more electrodes in thecase of an impedance-based localization system, one or more coils (i.e.,wire windings) configured to detect one or more characteristics of amagnetic field, for example in the case of a magnetic-field basedlocalization system, or a combination of impedance-based andmagnetic-field based localizations systems, such as, for example, theEnSite Precision™ system from St. Jude Medical, Inc.

Localization and navigation system 30 determines respective positions ofcatheter electrodes relative to the pulmonary vein within which catheter14 is positioned. The visualization system of localization andnavigations system 30 renders and displays the respective positions ofcatheter 14 and the catheter electrodes in two or three dimensions ondisplay 34 b. In certain embodiments, localization and navigation system30 enables a clinician or physician to visualize the locations of thecatheter electrodes relative to the pulmonary vein on display 34 b andto select a subset of the catheter electrodes using a user interface,such as, for example, input/output mechanisms 34 a. Localization andnavigation system 30 enables the clinician or physician to select asubset of electrodes to be energized based on a determination of whichelectrodes on catheter 14 form a most-concentric ring of electrodes withrespect to the central axis of the pulmonary vein. In certainembodiments, localization and navigation system 30 may propose a defaultsubset of electrodes on catheter 14 in lieu of a selection by theclinician or physician.

In alternative embodiments, localization and navigation system 30automatically determines which catheter electrodes should be energizedto achieve a ring of electrodes that is concentric with the central axisof the pulmonary vein. Such an automatic determination may be carriedout based on, for example, the determined respective positions of thecatheter electrodes, or respective contact of each electrode with thepulmonary vein. For example, in one embodiment, localization andnavigation system 30 determines which electrodes form an approximatelycircular or ellipsoid closed path. In some embodiments, the path isapproximately orthogonal to the ostium or antrum of the pulmonary veinbeing ablated, i.e., the electrodes would lie on a plane that isapproximately orthogonal to the central axis of the pulmonary vein. Sucha selection may improve the success rate of the ablation procedure. Thecircular or ellipsoid closed path is found by approximating the catheteras an ellipsoid, a plane is identified that is approximately orthogonalto the pulmonary vein, and an intersection of the plane and ellipsoid iscomputed according to, for example, P. Klein, On the Ellipsoid and PlaneIntersection Equation, Applied Mathematics, Vol. 3 No. 11, 2012, pp.1634-1640.

The ellipsoid that models a basket, balloon, or helical catheter isexpressed as, for example:

$\begin{matrix}{{\frac{x^{2}}{a^{2}} + \frac{y^{2}}{b^{2}} + \frac{z^{2}}{c^{2}}} = 1} & {{EQ}.1}\end{matrix}$where, a, b, and c represent the major axes of the ellipsoid.

The plane that intersects the ellipsoid is expressed as, for example:n(x−x ₀)=0  EQ. 2where n is the normal vector of the plane and represents the centralaxis of the pulmonary vein, and x₀ is an intersection point throughwhich the plane passes. In an alternative embodiment, the orientation ofthe plane is user-controlled and may be selected such that the plane isoriented with normal vector, n, misaligned from the central axis of thepulmonary vein. In such an embodiment, a graphical user interface may beprovided that enables rotation of the plane with respect to theellipsoid that represents the catheter, thus enabling the user to selectthe shape and orientation of the lesion.

The intersection of a plane and an ellipsoid is illustrated in FIG. 7 ,which shows a plot 700 of an ellipsoid 702 and an intersecting plane704. The intersection point, x₀, defines the depth of the lesion, whichcan be set more distally or more proximally along the central axis 706of the pulmonary vein. Given a value for x₀, the plane is expressed as:dx+ey+fz+g=0  EQ. 3

Referring to FIG. 7 , the axes of ellipsoid 702 define a coordinateframe. The plane defined in EQ. 3 is then rotated into the coordinateframe defined by the axes of ellipsoid 702.

Generally, the intersection of a plane and an ellipsoid is an ellipse.Such an ellipse generally does not pass exactly through locations ofelectrodes on the catheter. The catheter electrodes approximate theellipse to form the closed path. In one embodiment, electrodes within athreshold distance of the plane are selected. In some embodiments, thethreshold distance may be defined, for example, as 4.0 mm. In analternative embodiment, electrodes are selected that are closest to theellipse that defines the intersection. In such an embodiment, theelectrodes are identified by an iterative search, such as, for example,using the gradient decent method. Accordingly, the value of the searchdistance defines the width of the elliptical path and therefore thelesion. For example, a search distance of 10 mm would yield a widerlesion than a search distance of 4.0 mm.

In certain embodiments, localization and navigation system 30 mayinclude a contact sensing system such as, for example, an electricalimpedance sensing system that determines whether a given electrode is incontact with the pulmonary vein. In such embodiments, localization andnavigation system 30 considers whether a given electrode is in contactwith the pulmonary vein in selecting the subset of catheter electrodes.Electrode-tissue contact may be determined using various technologies,including, for example, imaging, electrogram amplitude, impedancemeasuring, contact force sensing, ultrasound based distance measurement(e.g., m-mode), and temperature based contact sensing. Temperature basedcontact sensing operates on the principal that, when an RF current issupplied through the electrodes, electrodes in the blood are cooled andmaintain a relatively stable temperature, while electrodes contactingthe endocardium typically rise in temperature.

FIG. 2 is a schematic diagram of an exemplary basket catheter 200 foruse in electroporation system 10, shown in FIG. 1 . Basket catheter 200includes shaft 44 illustrated at distal section 48 and, morespecifically, at the distal end, to which electrode assembly 12 iscoupled. Electrode assembly 12 includes a structure composed of aplurality of splines 202. Each spline 202 of the plurality includesmultiple electrodes 204 configured to be individually and selectivelyenergized. Splines 202 define a first pole 206 and a second pole 208 atwhich splines 202 are joined.

Electrodes 204 are configured for use as electroporation electrodes. Insome embodiments, electrodes 204 may be configured for additional uses.For example, one or more of electrodes 204 may perform a location orposition sensing function. More particularly, one or more of electrodes204 may be configured to be a positioning sensor(s) that providesinformation relating to the location (position and orientation) ofcatheter 14, and distal section 48 of shaft 44 thereof, in particular,at certain points in time. Accordingly, as catheter 14 is moved along asurface of a structure of interest of tissue 16 and/or about theinterior of the structure, the sensor(s) can be used to collect locationdata points that correspond to the surface of, and/or other locationswithin, the structure of interest. These location data points can thenbe used by, for example, a model construction system, in theconstruction of a three-dimensional model of the structure of interest.In other embodiments, separate catheter electrodes are used forelectroporation and positioning.

Electrodes 204 may be evenly distributed about splines 202. Electrodes204, in the embodiment of FIG. 2 , include flexible circuitsrespectively coupled to the electrodes and powered by conductors housedwithin shaft 44. Electrodes 204, in alternative embodiments, areplatinum ring electrodes configured to conduct and/or dischargeelectrical current in the range of one thousand volts and/or tenamperes. In certain embodiments, splines 202 of basket catheter 200 arehelical splines that rotate about a central axis of electrode assembly12. Such a helical configuration distributes electrodes 204 moreuniformly over the surface of basket catheter 200. In other embodiments,basket catheter 200 may include any suitable number of electrodes 204made of any suitable material. Electrodes 204 may comprise any catheterelectrode suitable to conduct high voltage and/or high current (e.g., inthe range of one thousand volts and/or ten amperes). Each catheterelectrode 204 is separated from each other catheter electrode by aninsulated gap 210. In the example embodiment, each electrode 204 has asame length 212 and each insulated gap 210 has a same length as eachother gap 210. In other embodiments, lengths of electrodes 204 andinsulated gap 210 may be different from each other. Moreover, in someembodiments, electrodes 204 may not all have the same length 212 and/orinsulated gaps 210 may not all have the same length. In someembodiments, electrodes 204 are not evenly distributed about splines202.

FIG. 3 is a schematic diagram of an exemplary visualization 300 of anexemplary electrode assembly 12 for use in basket catheter 200, shown inFIG. 2 . Electrode assembly 12 is positioned in a pulmonary vein 302.Pulmonary vein 302 defines a central axis 304. Electrode assembly 12includes a plurality of electrodes 204 distributed about splines 202.Splines 202 define first and second poles 206 and 208 where splines 202join. Electrodes 204 are not evenly distributed about splines 202.Electrodes 204 are concentrated away from first and second poles 206 and208, because first and second poles 206 and 208 are unlikely to makecontact with pulmonary vein 302 when basket catheter 200 is positioned.In other words, electrodes 204 are more likely to contact pulmonary vein302 when concentrated away from first and second poles 206 and 208.

Visualization 300 illustrates a subset of electrodes 306 that areselected from among electrodes 204. Subset of electrodes 306 may beselected automatically, as described above, or by a user such as aclinician or physician. In certain embodiments, subset of electrodes 306is initially selected automatically by localization and navigationsystem 30 based on, for example, each electrode's contact state, andproposed to the clinician or physician operating the system. The systemthen enables the clinician or physician to confirm or modify the subsetof electrodes 306. Subset of electrodes 306 is selected such thatelectrodes 306 form a path through electrodes 306 that best-approximatesa great circle around basket catheter 200 and, further, form a ring ofelectrodes 306 that is most-concentric with central axis 304 ofpulmonary vein 302. Such a ring may, under certain circumstances, besubstantially circular or, under certain circumstances, be non-circular.When energized, electrodes 306 form a virtual spiral catheter thatdelivers DC energy in approximately the same geometric pattern as wouldbe accomplished with an ideally-placed hoop or spiral catheter.

In alternative embodiments, a more-dense array of electrodes 204 isprovided on electrode assembly 12 to enable selection of the subset ofelectrodes 306 that is more concentric with central axis 304 ofpulmonary vein 302. Embodiments having fewer electrodes 204 availablefor selection enable selection of a more approximately concentric ringof electrodes 306.

Visualization 300 further illustrates a user interface 308 foruser-selection of the subset of electrodes 306. User interface 308 maybe integrated within localization and navigation system 30, shown inFIG. 1 , as well as with the visualization system for three-dimensionalor two-dimensional display of electrode assembly 12 within pulmonaryvein 302.

FIG. 4 is a schematic diagram of an exemplary balloon catheter 400 foruse in electroporation system 10, shown in FIG. 1 . Balloon catheter 400includes a balloon surface 402 expanding from distal section 48 ofcatheter 14, shown in FIG. 1 . Balloon catheter 400 includes electrodeassembly 12 having multiple electrodes 404 printed on balloon surface402. Each of electrodes 404 is configured to be individually andselectively energized to form a ring of electrodes that is concentricwith central axis 304 of pulmonary vein 302, both shown in FIG. 3 .

FIG. 5 is a schematic diagram of an exemplary helical catheter 500 foruse in electroporation system 10, shown in FIG. 1 . Helical catheter 500includes a plurality of helical splines 502 that rotate about a centralaxis 504 and join at an end 506. A plurality of electrodes (not shown)are distributed over helical splines 502 to form electrode assembly 12.Each of the electrodes is configured to be individually and selectivelyenergized to form a ring of electrodes that is concentric with centralaxis 304 of pulmonary vein 302, both shown in FIG. 3 .

FIG. 6 is a flow diagram of an exemplary method 600 of energizingcatheter 14 and, more specifically, electrode assembly 12, shown inFIGS. 1-4 . Referring to FIGS. 1-6 , method 600 begins with positioning610 distal section 48 of catheter 14 relative to a central axis inspace, such as, for example, central axis 304 defined by pulmonary vein302. Distal section 48 is maneuverable to position electrode assembly12, including electrodes 204, which are distributed about a structure ofelectrode assembly 12. The structure of electrode assembly 12 mayinclude, for example, splines 202 or balloon surface 402. The structureof electrode assembly 12 at least partially surrounds the central axis.

Once catheter 14 is positioned 610, localization and navigation system30 determines 620 respective locations of the plurality of electrodes204 relative to the central axis. A subset of electrodes 306 is thenselected 630 based on the respective locations of electrodes 204.Electrodes 306 form a circumferential ring of electrodes that isconcentric with the central axis and may be substantially circular ornon-circular. Localization and navigation system 30 is configured toselect 630 electrodes 306 and to control electroporation generator 26 toenergize 640 subset of electrodes 306. Selecting 630 electrodes 306 andenergizing 640 electrodes 306 may be carried out by electroporationgenerator 26 by controlling a network of switches or an addressingcircuit that enables the generated DC signal to reach electrodes 306through shaft 44 to electrode assembly 12 at distal section 48.Accordingly, electroporation generator 26 is further controlled bylocalization and navigation system 30 to ensure the remaining electrodesof the plurality of electrodes 204 are not energized or, alternatively,the remaining electrodes may be utilized as return electrodes.

The technical effects of the embodiments described above may include:(a) reducing the time necessary to properly position a catheter fordelivering electroporation to cardiac tissue; (b) improvingconcentricity of circumferential lesions with respect to the centralaxis of targeted veins; (c) improving effectiveness of electroporationtherapy; (d) reducing the overall time of electroporation treatmentsessions; (e) simplifying positioning of a catheter for deliveringelectroporation through use of a basket catheter or a balloon catheterin a collapsed state; and (f) improving respective contact of catheterelectrodes to cardiac tissue through use of a basket catheter or aballoon catheter.

Although certain embodiments of this disclosure have been describedabove with a certain degree of particularity, those skilled in the artcould make numerous alterations to the disclosed embodiments withoutdeparting from the spirit or scope of this disclosure. All directionalreferences (e.g., upper, lower, upward, downward, left, right, leftward,rightward, top, bottom, above, below, vertical, horizontal, clockwise,and counterclockwise) are only used for identification purposes to aidthe reader's understanding of the present disclosure, and do not createlimitations, particularly as to the position, orientation, or use of thedisclosure. Joinder references (e.g., attached, coupled, connected, andthe like) are to be construed broadly and may include intermediatemembers between a connection of elements and relative movement betweenelements. As such, joinder references do not necessarily infer that twoelements are directly connected and in fixed relation to each other. Itis intended that all matter contained in the above description or shownin the accompanying drawings shall be interpreted as illustrative onlyand not limiting. Changes in detail or structure may be made withoutdeparting from the spirit of the disclosure as defined in the appendedclaims.

When introducing elements of the present disclosure or the preferredembodiment(s) thereof, the articles “a”, “an”, “the”, and “said” areintended to mean that there are one or more of the elements. The terms“comprising”, “including”, and “having” are intended to be inclusive andmean that there may be additional elements other than the listedelements.

As various changes could be made in the above constructions withoutdeparting from the scope of the disclosure, it is intended that allmatter contained in the above description or shown in the accompanyingdrawings shall be interpreted as illustrative and not in a limitingsense.

What is claimed is:
 1. A catheter for delivering electroporation, thecatheter comprising: a distal section configured to be positioned in avein within a body, the vein defining a central axis; and an electrodeassembly coupled to the distal section, the electrode assemblycomprising: a structure configured to at least partially contact thevein, and a plurality of electrodes distributed about the structure,each electrode of the plurality of electrodes configured to beselectively energized to form a circumferential ring of energizedelectrodes that is concentric with the central axis of the vein, whereina subset of the plurality of electrodes that forms the circumferentialring is configured to be selected by a computing system coupled to thecatheter by automatically determining, based on detected respectivepositions of the plurality of electrodes, which of the plurality ofelectrodes form an approximately circular or ellipsoid closed path,wherein the computing system is configured to automatically determinewhich of the plurality of electrodes form an approximately circular orellipsoid closed path by: approximating the catheter as an ellipsoid;identifying, based on user input received at the computing system, aplane oriented perpendicular to a normal vector; computing anintersection between the ellipsoid and the identified plane; andselecting electrodes of the plurality of electrodes that are within athreshold distance of the computed intersection.
 2. The catheter ofclaim 1, wherein the structure comprises a balloon around which theplurality of electrodes are distributed.
 3. The catheter of claim 1,wherein the structure comprises a basket having a plurality of splinesalong which the plurality of electrodes is distributed.
 4. The catheterof claim 3, wherein the plurality of splines define first and secondpoles at which the plurality of splines join, and wherein the pluralityof electrodes are concentrated away from the first and second poles. 5.The catheter of claim 1, wherein the circumferential ring of energizedelectrodes is non-circular.
 6. An electroporation system comprising: acatheter comprising an electrode assembly configured to be positioned ina vein of a body, the vein defining a central axis, the electrodeassembly comprising: a structure configured to at least partiallycontact the vein, and a plurality of electrodes distributed about thestructure, each electrode of the plurality of electrodes configured tobe individually energized; a direct current (DC) energy source coupledto the catheter and configured to selectively energize a subset ofelectrodes of the plurality of electrodes; and a computing systemcoupled to the catheter and the DC energy source, the computing systemconfigured to: detect respective positions of the plurality ofelectrodes within the vein, and select the subset of electrodes to forma circumferential ring of energized electrodes that is concentric withthe central axis of the vein, the computing system configured to selectthe subset of electrodes by automatically determining, based on thedetected respective positions, which of the plurality of electrodes forman approximately circular or ellipsoid closed path, wherein thecomputing system is configured to automatically determine which of theplurality of electrodes form an approximately circular or ellipsoidclosed path by: approximating the catheter as an ellipsoid; identifyinga plane that is approximately orthogonal to the central axis of thevein; computing an intersection between the ellipsoid and the identifiedplane; and selecting, using an iterative search, electrodes of theplurality of electrodes that are closest to the computed intersection.7. The electroporation system of claim 6, wherein the computing systemfurther comprises a visualization system configured to display therespective positions of the plurality of electrodes with respect to thevein.
 8. The electroporation system of claim 7, wherein thevisualization system is further configured to render a three-dimensionaldisplay.
 9. The electroporation system of claim 7, wherein the computingsystem further comprises a user interface configured to enable userselection of the subset of electrodes.
 10. The electroporation system ofclaim 6, wherein the computing system is further configured to detectrespective contact of the plurality of electrodes with the vein.
 11. Amethod of energizing a catheter, the method comprising: positioning adistal section of the catheter relative to a central axis in space, thedistal section comprising a plurality of electrodes distributed about astructure, the structure at least partially surrounding the centralaxis; determining respective locations of the plurality of electrodesrelative to the central axis; selecting, using a computing device, asubset of electrodes from among the plurality of electrodes byautomatically detecting, based on the determined respective locations,which of the plurality of electrodes form an approximately circular orellipsoid closed path, the subset of electrodes forming acircumferential ring of electrodes that is concentric with the centralaxis, wherein the computing device is configured to automatically detectwhich of the plurality of electrodes form an approximately circular orellipsoid closed path by: approximating the catheter as an ellipsoid;identifying, based on user input received at the computing system, aplane oriented perpendicular to a normal vector; computing anintersection between the ellipsoid and the identified plane; andselecting, using an iterative search, electrodes of the plurality ofelectrodes that are closest to the computed intersection; and energizingthe subset of electrodes.
 12. The method of claim 11 further comprisingdisplaying the respective positions of the plurality of electrodes on avisualization system.
 13. The method of claim 11, wherein the cathetercomprises a basket catheter, the method further comprising expanding thebasket catheter relative to the central axis after positioning thedistal section.
 14. The method of claim 11, wherein energizing thesubset of electrodes comprises: generating a direct current (DC) signal;conducting the DC signal through the catheter to the subset ofelectrodes; and de-energizing remaining electrodes of the plurality ofelectrodes.
 15. The method of claim 11, wherein the catheter comprises aballoon catheter, the method further comprising expanding the ballooncatheter relative to the central axis after positioning the distalsection.